DNAH11

Last updated

DNAH11
Identifiers
Aliases DNAH11 , CILD7, DNAHBL, DNAHC11, DNHBL, DPL11, dynein axonemal heavy chain 11
External IDs OMIM: 603339; MGI: 1100864; HomoloGene: 2801; GeneCards: DNAH11; OMA:DNAH11 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001277115

NM_010060

RefSeq (protein)

NP_001264044

n/a

Location (UCSC) Chr 7: 21.54 – 21.9 Mb Chr 12: 117.84 – 118.16 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Dynein axonemal heavy chain 11 (DNAH11) is a protein that is encoded by the DNAH11 gene in humans. [5] [6] In mice, the protein is encoded by the Dnahc11 gene, the murine homolog to human DNAH11. [7] The protein was previously known as 'left-right' dynein (with the corresponding gene alias lrd) in mice and is particularly notable during embryogenesis for orientation of the eventual body plan. [8] [9]

Contents

Function

This gene encodes a member of the dynein heavy chain family, DNAH11, a microtubule-dependent motor ATPase protein critical for processes involving ciliary movement. The gene DNAH11 has reported associations in a number of important physiological processes including the movement of respiratory cilia, sperm motility, and establishment of the adult body plan. [7] [10] [11] [12] A knockout model of this gene has not been reported.

Embryogenesis

The body plan is naturally asymmetrical, and the overall order is defined during embryonic gastrulation in mammals where the three germ layers (endoderm, mesoderm, and ectoderm) are established. At the beginnings of gastrulation, the primitive node serves as the organizer and has motile cilia on its surface. [13] [14] These cilia are responsible for directing increased amounts of nodal to the left side of the developing embryo, establishing asymmetry. [7] For this reason, proper expression of DNAH11 is critical for correct establishment and subsequent development of the asymmetrical body plan.

Clinical significance

Primary ciliary dyskinesia

Mutations in this DNAH11 have been implicated in causing Primary Ciliary Dyskinesia (PCD), formerly called 'immotile cilia syndrome', and results from abnormally motile or static cilia within the respiratory tract. [7] PCD is characterized by bronchiectasis, frequent upper respiratory tract infections, and issues with fertility, and PCD individuals have increased rates of heterotaxy and situs inversus in approximately 50% of reported cases, a congenital condition in which some organs are mirrored to an abnormal side of the body cavity. [15] [16] Mutations in DNAH11 are also associated with Kartagener syndrome (PCD with situs inversus totalis, a congenital condition with a characteristic total inversion of the body plan and organs). [15]

Fertility

Genetic errors with DNAH11 have been shown to cause a number of fertility-related effects in both sexes. Decreased motile cilia-specific expression of DNAH11 within the axoneme of sperm is associated with lower levels of sperm motility. [17] [18] For this reason, males with PCD are not sterile, but they are often infertile under conventional methods due to lack of sperm motility; [6] [18] however, there are cases of DNAH11 mutant males fathering offspring without intervention of assisted reproductive technologies. [19] [20] In females with PCD or Kartagener's syndrome, there are increased reports of subfertility and risk of ectopic pregnancy. [21] [22] Because females' fallopian tubes are lined with motile cilia which show identical motor protein composition to those observed in the respiratory tract, this is believed to result in the increased risks observed in case studies (although affected PCD females' cilia have not been directly analyzed so this remains inconclusive). [23]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000105877 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000018581 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Chapelin C, Duriez B, Magnino F, Goossens M, Escudier E, Amselem S (Sep 1997). "Isolation of several human axonemal dynein heavy chain genes: genomic structure of the catalytic site, phylogenetic analysis and chromosomal assignment". FEBS Letters. 412 (2): 325–330. Bibcode:1997FEBSL.412..325C. doi:10.1016/S0014-5793(97)00800-4. PMID   9256245. S2CID   23935907.
  6. 1 2 "Entrez Gene: DNAH11 dynein, axonemal, heavy chain 11".
  7. 1 2 3 4 Lucas, J. S., Adam, E. C., Goggin, P. M., Jackson, C. L., Powles‐Glover, N., Patel, S. H., ... & Lackie, P. M. (2012). Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD. Human mutation, 33(3), 495-503. https://doi.org/10.1002/humu.22001
  8. Supp, D. M., Brueckner, M., Kuehn, M. R., Witte, D. P., Lowe, L. A., McGrath, J., ... & Potter, S. S. (1999). Targeted deletion of the ATP binding domain of left-right dynein confirms its role in specifying development of left-right asymmetries. Development, 126(23), 5495-5504. https://doi.org/10.1242/dev.126.23.5495
  9. Xia, H., Huang, X., Deng, S., Xu, H., Yang, Y., Liu, X., ... & Deng, H. (2021). DNAH11 compound heterozygous variants cause heterotaxy and congenital heart disease. PLoS One, 16(6), e0252786. https://doi.org/10.1371/journal.pone.0252786
  10. Zhu D, Zhang H, Wang R, Liu X, Jiang Y, Feng T, et al. (June 2019). "Association of DNAH11 gene polymorphisms with asthenozoospermia in Northeast Chinese patients". Bioscience Reports. 39 (6). doi:10.1042/bsr20181450. ISSN   0144-8463. PMC   6617048 . PMID   31160482.
  11. Zariwala MA, Knowles MR, Omran H (2007-03-01). "Genetic Defects in Ciliary Structure and Function" . Annual Review of Physiology. 69 (1): 423–450. doi:10.1146/annurev.physiol.69.040705.141301. ISSN   0066-4278. PMID   17059358.
  12. Wagner MK, Yost HJ (2000-02-15). "Left–right development: The roles of nodal cilia". Current Biology. 10 (4): R149 –R151. Bibcode:2000CBio...10.R149W. doi: 10.1016/S0960-9822(00)00328-6 . ISSN   0960-9822. PMID   10704402.
  13. Harvey RP (1998-08-07). "Links in the Left/Right Axial Pathway". Cell. 94 (3): 273–276. doi: 10.1016/S0092-8674(00)81468-3 . ISSN   0092-8674. PMID   9708727.
  14. Grabowski CT (August 1962). "Neural induction and notochord formation by mesoderm from the node area of the early chick blastoderm" . The Journal of Experimental Zoology. 150 (3): 233–245. Bibcode:1962JEZ...150..233G. doi:10.1002/jez.1401500307. ISSN   0022-104X. PMID   13949682.
  15. 1 2 Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, Scamuffa N, et al. (2002-08-06). "Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia". Proceedings of the National Academy of Sciences of the United States of America. 99 (16): 10282–10286. Bibcode:2002PNAS...9910282B. doi: 10.1073/pnas.152337699 . ISSN   0027-8424. PMC   124905 . PMID   12142464.
  16. Russakoff AH, Katz HW (1946-08-22). "Dextrocardia and Bronchiectasis: A Review of the Literature and a Report of Two Cases" . The New England Journal of Medicine. 235 (8): 253–255. doi:10.1056/NEJM194608222350803. ISSN   0028-4793. PMID   20996259.
  17. Whitfield M, Thomas L, Bequignon E, Schmitt A, Stouvenel L, Montantin G, et al. (2019-07-03). "Mutations in DNAH17, Encoding a Sperm-Specific Axonemal Outer Dynein Arm Heavy Chain, Cause Isolated Male Infertility Due to Asthenozoospermia". American Journal of Human Genetics. 105 (1): 198–212. doi:10.1016/j.ajhg.2019.04.015. ISSN   0002-9297. PMC   6612517 . PMID   31178125.
  18. 1 2 Sironen A, Shoemark A, Patel M, Loebinger MR, Mitchison HM (2019-11-28). "Sperm defects in primary ciliary dyskinesia and related causes of male infertility". Cellular and Molecular Life Sciences. 77 (11): 2029–2048. doi:10.1007/s00018-019-03389-7. ISSN   1420-682X. PMC   7256033 . PMID   31781811.
  19. Vanaken GJ, Bassinet L, Boon M, Mani R, Honoré I, Papon JF, et al. (2017-11-01). "Infertility in an adult cohort with primary ciliary dyskinesia: phenotype–gene association". The European Respiratory Journal. 50 (5). doi: 10.1183/13993003.00314-2017 . ISSN   0903-1936. PMID   29122913.
  20. Schwabe GC, Hoffmann K, Loges NT, Birker D, Rossier C, de Santi MM, et al. (February 2008). "Primary ciliary dyskinesia associated with normal axoneme ultrastructure is caused byDNAH11mutations". Human Mutation. 29 (2): 289–298. doi:10.1002/humu.20656. ISSN   1059-7794. PMID   18022865. S2CID   22292489.
  21. Blyth M, Wellesley D (April 2008). "Ectopic pregnancy in primary ciliary dyskinesia". Journal of Obstetrics and Gynaecology. 28 (3): 358. doi:10.1080/01443610802058742. PMID   18569496. S2CID   19624982.
  22. Halbert SA, Patton DL, Zarutskie PW, Soules MR (1997-01-01). "Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener's syndrome". Human Reproduction. 12 (1). Oxford, England: 55–58. doi: 10.1093/humrep/12.1.55 . ISSN   0268-1161. PMID   9043902.
  23. Raidt J, Werner C, Menchen T, Dougherty GW, Olbrich H, Loges NT, et al. (2015-09-15). "Ciliary function and motor protein composition of human fallopian tubes". Human Reproduction. 30 (12). Oxford, England: 2871–2880. doi: 10.1093/humrep/dev227 . ISSN   1460-2350. PMID   26373788.

Further reading